Peripheral CD56+CD16+ NK Cell Populations in the Early Follicular Phase Are Associated With Successful Clinical Outcomes of Intravenous Immunoglobulin Treatment in Women With Repeated Implantation Failure

Yao-Kai Ho; Hsiu-Hui Chen; Chun-Chia Huang; Chun-I Lee; Pin-Yao Lin; Maw-Sheng Lee; Tsung-Hsien Lee

doi:10.3389/fendo.2019.00937

Peripheral CD56⁺CD16⁺ NK Cell Populations in the Early Follicular Phase Are Associated With Successful Clinical Outcomes of Intravenous Immunoglobulin Treatment in Women With Repeated Implantation Failure

Front Endocrinol (Lausanne). 2020 Jan 21:10:937. doi: 10.3389/fendo.2019.00937. eCollection 2019.

Authors

Yao-Kai Ho^{1

2}, Hsiu-Hui Chen³, Chun-Chia Huang³, Chun-I Lee^{1

2

3}, Pin-Yao Lin^{1

3}, Maw-Sheng Lee^{1

2

3}, Tsung-Hsien Lee^{1

2

3}

Affiliations

¹ Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
² Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan.
³ Division of Infertility, Lee Women's Hospital, Taichung, Taiwan.

Abstract

The percentage of peripheral CD56⁺CD16⁺ NK cells in the early follicular phase on days 2-3 of the menstrual cycle in repeated implantation failure (RIF) patients was used to evaluate the impact of intravenous immunoglobulin (IVIG) on ART cycles. A total 283 patients with RIF consisting of at least 3 ART failures and at least 2 high quality embryo transfers were recruited. A logistic regression analysis for the peripheral immunological profile was completed to predict implantation success and compare the implantation and pregnancy rates between groups with ≤10.6 and >10.6% of CD56⁺CD16⁺ NK cells in the early follicular phase. The logistic regression and receiving operating curve analyses showed that patients with ≤ 10.6% of peripheral CD56⁺CD16⁺ NK cells in the early follicular phase showed a lower pregnancy rate within the RIF group without IVIG. Patients with peripheral CD56⁺CD16⁺ NK cells ≤ 10.6% and without IVIG treatment showed significantly lower implantation and pregnancy rates (12.3 and 30.3%, respectively) when compared with the CD56⁺CD16⁺ NK cells >10.6% group (24.9 and 48.0%, respectively, p < 0.05). Furthermore, the patients with CD56⁺CD16⁺ NK cells ≤ 10.6% given IVIG starting before ET had significantly higher implantation, pregnancy, and live birth rates (27.5, 57.4, and 45.6%, respectively) when compared with the non-IVIG group (12.3, 30.3, and 22.7%, respectively, p < 0.05). Our results showed that a low percentage of peripheral CD56⁺CD16⁺ NK cells (≤10.6%) in the early follicular phase is a potential indicator of reduced pregnancy and implantation success rates in RIF patients, and IVIG treatment will likely benefit this patient subgroup.

Keywords: infertility; intravenous immunoglobulin; lymphocytes; natural killer cells; repeated implantation failure.